[Paraneoplastic dermatomyositis related to breast cancer: rare clinical association in two patients]. / Dermatomiositis paraneoplásica relacionada a cáncer de mama: asociación clínica en dos pacientes.

Paraneoplastic dermatomyositis is an inflammatory disease of the connective tissue that is caused by inmmunologic events in the presence of malignant tumors. It is more likely to happen in middle aged women and is related to ovarian, pancreatic, stomach and colon cancer and non Hogdkin lymphoma. We present two cases of dermatomyositis, with amyopathic origin associated to breast cancer. The first case occurs as the neoplasia evolves and the second one as an initial manifestation that leads to the search and subsequent diagnosis of cancer.

[Subacute diseminated histoplasmosis in HIV patients]. / Histoplasmosis diseminada subaguda en pacientes VIH.

Histoplasmosis is a cosmopolitan mycosis caused by Histoplasma capsulatum. It is endemic of Río de la Plata's riverbed and in immunocompromised patients may be deadly. We present two patients with Human Immunodeficiency Virus diagnosed with subacute disseminated histoplasmosis, which is a marker of Acquired Human Immunodeficiency Syndrome. This situation increases the morbimortality, thus forcing clinicians to diagnose and treat rapidly in order to avoid fatal outcomes.

La histoplasmosis es una micosis cosmopolita causada por el Histoplasmacapsulatum. Es un hongo endémico de la cuenca del Río de La Plata que si afecta a inmunosuprimidos puede ser mortal. Presentamos dos pacientes con Virus de Inmunodeficiencia Humana con diagnóstico de histoplasmosis diseminada subaguda. Esta situación los cataloga en estadío de Síndrome de Inmunodeficiencia Adquirida y requiere pronta acción médica para evitar complicaciones.

Mesenchymal stem cells (MSCs) from scleroderma patients (SSc) preserve their immunomodulatory properties although senescent and normally induce T regulatory cells (Tregs) with a functional phenotype: implications for cellular-based therapy.

Systemic sclerosis (SSc) is a chronic disease, with early activation of the immune system. The aim of our work was to address how SSc-mesenchymal stem cells (MSCs), although senescent, might preserve specific immunomodulatory abilities during SSc. MSCs were obtained from 10 SSc patients and 10 healthy controls (HC). Senescence was evaluated by assessing cell cycle, ß-galactosidase (ß-Gal) activity, p21 and p53 expression; doxorubicin was used as acute senescence stimulus to evaluate their ability to react in stressed conditions. Immunomodulatory abilities were studied co-culturing MSCs with peripheral blood mononuclear cells (PBMCs) and CD4(+) cells, in order to establish both their ability to block proliferation in mixed lymphocyte reaction and in regulatory T cells (Tregs) induction. SSc-MSC showed an increase of senescence biomarkers. Eighty per cent of MSCs were in G0-G1 phase, without significant differences between SSc and HC. SSc-MSCs showed an increased positive ß-Gal staining and higher p21 transcript level compared to HC cells. After doxorubicin, ß-Gal staining increased significantly in SSc-MSCs. On the contrary, doxorubicin abolished p21 activation and elicited p53 induction both in SSc- and HC-MSCs. Interleukin (IL)-6 and transforming growth factor (TGF)-ß-related transcripts and their protein levels were significantly higher in SSc-MSCs. The latter maintained their immunosuppressive effect on lymphocyte proliferation and induced a functionally regulatory phenotype on T cells, increasing surface expression of CD69 and restoring the regulatory function which is impaired in SSc. Increased activation of the IL-6 pathway observed in our cells might represent an adaptive mechanism to senescence, but preserving some specific cellular functions, including immunosuppression.

Immunomagnetic isolation of CD4+CD25+FoxP3+ natural T regulatory lymphocytes for clinical applications.

Although CD4(+)/CD25(+) T regulatory cells (T(regs)) are a potentially powerful tool in bone marrow transplantation, a prerequisite for clinical use is a cell-separation strategy complying with good manufacturing practice guidelines. We isolated T(regs) from standard leukapheresis products using double-negative selection (anti-CD8 and anti-CD19 monoclonal antibodies) followed by positive selection (anti-CD25 monoclonal antibody). The final cell fraction (CD4(+)/CD25(+)) showed a mean purity of 93.6% +/- 1.1. Recovery efficiency was 81.52% +/- 7.4. The CD4(+)/CD25(+bright) cells were 28.4% +/- 6.8. The CD4(+)/CD25(+) fraction contained a mean of 51.9% +/- 15.1 FoxP3 cells and a mean of 18.9% +/- 11.5 CD127 cells. Increased FoxP3 and depleted CD127 mRNAs in CD4(+)CD25(+)FoxP3(+) cells were in line with flow cytometric results. In Vbeta spectratyping the complexity scores of CD4(+)/CD25(+) cells and CD4(+)/CD25(-) cells were not significantly different, indicating that T(regs) had a broad T cell receptor repertoire. The inhibition assay showed that CD4(+)/CD25(+) cells inhibited CD4(+)/CD25(-) cells in a dose-dependent manner (mean inhibition percentages: 72.4 +/- 8.9 [ratio of T responder (T(resp)) to T(regs), 1:2]; 60.8% +/- 20.5 (ratio of T(resp) to T(regs), 1:1); 25.6 +/- 19.6 (ratio of T(resp) to T(regs), 1:0.1)). Our study shows that negative/positive T(reg) selection, performed using the CliniMACS device and reagents, enriches significantly CD4(+)CD25(+)FoxP3(+) cells endowed with immunosuppressive capacities. The CD4(+)CD25(+)FoxP3(+) population is a source of natural T(reg) cells that are depleted of CD8(+) and CD4(+)/CD25(-) reacting clones which are potentially responsible for triggering graft-versus-host disease (GvHD). Cells isolated by means of this approach might be used in allogeneic haematopoietic cell transplantation to facilitate engraftment and reduce the incidence and severity of GvHD without abrogating the potential graft-versus-tumour effect.

Mesenchymal cells: a vehicle for gene therapy.

T cell-depleted allogeneic stem cell transplantation is associated with delayed immunological reconstitution. Bone marrow stroma and interleukin 7 (IL-7) regulate homeostasis of T lymphocytes. We engineered human stromal cells with a retroviral vector containing the IL-7 gene and studied in vitro effects on T cells. Human stromal cells were successfully transduced and generated a layer that was morphologically and phenotypically normal. IL-7-engineered stromal cells conserve the biological properties of unmanipulated stromal cells. Through their production of IL-7, they enhance survival and homeostatic proliferation of naive T cells. Because of this cytokine production, they might be an ideal vehicle for gene therapy aimed at supporting lymphopoiesis in the T cell-deficient host.

Occult gastrointestinal bleeding in rugby player.

BACKGROUND: Local ischemia and mechanical trauma to hollow abdominal organs are quoted as a cause of gastrointestinal (GI) bleeding during and after long distance running. There are no data on athletes from rugby and other contact sports where mechanical trauma of the abdomen is frequent. METHODS: Occult bleeding in the stool of Croatian national rugby team players has been investigated during and after qualification match with Italy for the World Cup 1999 on June 6th 1998 in Makarska, Croatia. One player with positive test was followed and examined in detail after the game. RESULTS: Among 11 Croatian players authors discovered one with a history of GI symptoms and one with conversion of negative to positive test for occult bleeding in stool after the match. The latter player had no GI symptoms or diseases, took no medications, played only 20 minutes in the match on forward position. Conversion has been found in the second stool sample after game (24 to 48 hours after game). The athlete was followed for 18 months. Persistent low values of hemoglobin, hematocrit and serum iron were revealed, as well as expressed hemorrhoids without signs of haemorrhage or inflammation. CONCLUSIONS: Lower incidence of GI bleeding among rugby players than among long distance runners minimize the importance of mechanical abdominal trauma in the etiology of GI bleeding during sports activity. Hemorrhoids are not quoted as a cause of GI bleeding after sport activity among athletes.

Changes in characteristics of chronic pancreatitis during the course of disease.

Group of 100 patients with proven CP was analysed through the period of 5-20 years. According to duration of pancreatic disease patients were divided in three groups: 2-5 years from the onset of disease (12 patients), 5-8 years from the onset of disease (35 pts) and more than 8 years from the onset of disease (35 pts). At the start of the study all patients have refereed abdominal pain. Chymotripsin activity, BMI, patients' age, occurrence of diabetes and frequency of pain cessation between groups was compared. Significantly higher frequency of diabetics was found in group with longer duration of CP, as expected. Occurrence of pain declined significantly more often in those CP patients with associated diabetes as compared to those without diabetes. Cessation of pain was most prominent in patients with diabetes lasting for more than 8 years. Decline of pain frequency in CP patients despite the progressive pancreatic damage seems to be caused primarily by microvascular changes similar or identical to those occurring in diabetes.

[Surgical treatment of varicocele. Our experience in the last 10 years]. / Trattamento chirurgico del varicocele. Nostra esperienza negli ultimi 10 anni.

UNLABELLED: Varicocele means a varicose dilatation with stretching of the veins in the pampiniform plexus. In the last years the problem of varicocele has emerged again in all its importance for the increasing of couple sterility which, in Italy, is certified to 13%. It is known that this problem is connected to anomalies of the spermiogram, even in the subclinical forms located with the ultrasound method, and that the surgical operation allows to correct in a high percentage of cases. MATERIALS AND METHODS: For treatment of varicocele we use a technique with inguinal approach of 5-6 cm and isolation of all the dilated veins intra- and extrafunicular. After their ligation and section we transpose the funiculus proximally with a little traction on the testicle and we fix it to the great oblique muscle fascia, using margin of cremasteric muscle prepared in advance and distal stumps of resected veins. This manoeuvre forms a short ansa of the funiculus that, in the orthostatic position, helgs to stop the hematic column which weighs on the testicle. This operation has been performed in 54 patients. In 18 (60%), oligoastenospermia was present and 10 (33%) had consulted their physician for sterility problems (4 of them with a sub-clinical varicocele). The patients have been recalled for clinical and echo-doppler control as well qualitative evaluation of the sperm. The follow-up goes from 8 months to 7 years. RESULTS: We have noticed the presence of six relapses (13.3%) so divided: 4 relapses with a first grade reflux; 1 relapse with a second grade reflux and 1 relapse with a third grade reflux. Only in two patients with first grade reflux was the spermiogram normal, while in all the others oligoastenospermia persisted. Seric evaluation of testosterone and androstenedione have excluded hormonal causes of sterility. Among the 10 sterile patients 6 (60%), had a normalization of the spermiogram and 4 of them (2 of which with preceding subclinical varicocele), had a partner pregnancy in periods within 7 and 18 months after the operation. CONCLUSION: On the basis their experience, the authors confirm the validity of the selective varicocelectomy by inguinal approach, with probable further advantage using funicular transposition. To agree with other authors there isn't any very important advantage, in the cost/benefit ratio, between microsurgical diversion and laparoscopic surgery, and traditional varicocelectomy in local anesthesia. The incidence of relapses noticed (13.3%), lower than that rated at the high ligature (29%), is the expression of the anatomic complexity of the spermatic venous drainage, in such a way to think right a phlebographic anterograde intraoperative evaluation. We also confirm the importance of ultrasonographic and ecographic methods in the pre and postoperative evaluation, we underline that, in the subclinical cases, it is possible to verify spermiogram alteration corrected, in a high percentage, by varicocelectomy.

Pirenzepin in gastric and duodenal ulcer: a double-blind trial.

In seventy-five out-patients with gastric and duodenal ulcer a comparative double-blind trial with pirenzepin against placebo was performed. The dose was 50 mg pirenzepin daily or placebo respectively, the duration of treatment being 4 weeks. The healing effect of pirenzepin in duodenal ulcer patients could be proven endoscopically and was statistically significant when compared with placebo (p less than or equal to 0.05). Strong evidence for the therapeutic efficacy of pirenzepin could be further demonstrated in both duodenal and gastric ulcer patients by measuring the marked reduction of ulcer size, even though statistical difference against placebo in gastric ulcers was not fully achieved. Pirenzepin was well tolerated by all patients, except for a mild case of diarrhoea which occurred in one patient. No patient complained of dryness of the mouth or of blurred vision.